scholarly journals TNF-Alpha Inhibitors for Chronic Urticaria: Experience in 20 Patients

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Freja Lærke Sand ◽  
Simon Francis Thomsen

Patients with severe chronic urticaria may not respond to antihistamines, and other systemic treatment options may either be ineffective or associated with unacceptable side effects. We present data on efficacy and safety of adalimumab and etanercept in 20 adult patients with chronic urticaria. Twelve (60%) patients obtained complete or almost complete resolution of urticaria after onset of therapy with either adalimumab or etanercept. Further three patients (15%) experienced partial response. Duration of treatment ranged between 2 and 39 months. Those responding completely or almost completely had a durable response with a mean of 11 months. Six patients (30%) experienced side effects and five patients had mild recurrent upper respiratory infections, whereas one patient experienced severe CNS toxicity that could be related to treatment with TNF-alpha inhibitor. Adalimumab and etanercept may be effective and relatively safe treatment options in a significant proportion of patients with chronic urticaria who do not respond sufficiently to high-dose antihistamines or in whom standard immunosuppressive drugs are ineffective or associated with unacceptable side effects.

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S730-S730
Author(s):  
Shelbye R Herbin ◽  
Amina Ammar ◽  
Ryan Gumbleton ◽  
Jing Zhao ◽  
Shannon Olson ◽  
...  

Abstract Background Acinetobacter (ACB) infections are difficult to treat due to increasing drug resistance. The aim of this study is to evaluate the effectiveness of high-dose (HD) minocycline (MIN) 200mg q12h for the treatment of ACB infections Methods This is a retrospective study of pts with ACB from 1/1/19 to 10/31/20. Exclusions included non-susceptibility to MIN, age < 18 yrs, hospice care w/in 72 hrs of culture, or urine source. Use of HD MIN (IV or PO), was compared to alternative treatment (AT). Clinical and micro success at the end of therapy (EOT) was evaluated. Clinical success was elimination or improvement in signs and symptoms of infection. Micro success was eradication of ACB from the same site of infection at EOT. Length of stay (LOS), 30-day readmission (with or without ACB), isolation of a MIN non-susceptible ACB within 30 days of EOT, and adverse events related to MIN, were evaluated. Results A total of 320 pts were screened with the most common exclusion being MIN non-susceptible isolate. Of the 204 pts included, 38 received HD MIN and 166 received AT. The most common were cefepime (53/166) and meropenem (36/166). Median age (IQR) was 41 (30-50) yrs for HD MIN vs. 40 (27-48) yrs for AT. Both groups were mostly male (HD MIN: 63% vs. AT: 60%) and respiratory was the most common site (HD MIN: 61% vs. AT: 60%). HD MIN group had 74% of cultures that were polymicrobial vs. 86% in AT group. Lack of clinical response at the EOT occurred in 42% of pts on HD MIN and 37% on AT. Infection related mortality occurred in 24% on HD MIN vs. 15% on AT. In HD MIN group, 16 pts had a repeat culture from the same site after treatment with 25% still positive for ACB. In the AT group 61 pts had a repeat culture and 28% were positive for ACB. Duration of treatment (9 [6-11] days vs. 10 [2-18] days) and LOS (16 [18.25-26.75] vs. 29 [14-49]) were shorter in the HD MIN group. There was only one adverse event reported with the use of HD MIN Conclusion Pts in the HD MIN group had shorter treatment duration and a shorter LOS. Pts who received HD MIN had a lower rate of clinical cure and a higher mortality rate compared to pts in the AT group. Reasons for this difference will need to be investigated further. HD MIN should be reserved for pts who are unable to tolerate other treatment options or who have an ACB resistant to other treatment options. Disclosures All Authors: No reported disclosures


2011 ◽  
Vol 26 (S2) ◽  
pp. 1359-1359
Author(s):  
P. Chandrappa ◽  
L. Ho

IntroductionPatients suffering from treatment-resistant schizophrenia pose a difficult therapeutic challenge. Although Clozapine is a well-established treatment in such cases, there is a significant proportion of patients who have to discontinue Clozapine due to life-threatening side-effects, despite achieving good therapeutic response. There is very limited literature on the therapeutic alternatives to Clozapine in the treatment of resistant schizophrenia.ObjectiveTo report a case of resistant schizophrenia responding to high dose Quetiapine, following discontinuation of Clozapine due to neutropenia.Clinical details of the case: We are presenting a case of a forty-two year old female patient with treatment resistant schizophrenia who achieved remission following treatment with Clozapine, but had to discontinue treatment due to neutropenia, which occurred on two occasions. Clozapine discontinuation resulted in rapid and severe relapse in her condition and re-admission to hospital. Quetiapine was initiated as this stage, but only partial improvement was noted at the manufacturer's stated maximum daily dose of 800 mg/day. Since the drug was being well tolerated the dose was gradually further increased.ResultsThe dose of Quetiapine was eventually increased up to 1400 mg/day, which produced significant response and the patient was discharged from hospital. Quetiapine at this dose was well tolerated with minimal side effects.ConclusionThe above report indicates that high-dose Quetiapine is a viable alternative to Clozapine in treating refractory schizophrenia. The findings from this report support further investigation of this approach in the form of larger scale clinical trials.


Blood ◽  
2021 ◽  
Author(s):  
Mohamad Mohty ◽  
Hervé Avet-Loiseau ◽  
Jean-Luc Harousseau

Multiple myeloma is usually considered as an incurable disease. However, with the therapeutic improvement observed in the last few years, achievement of an "operational" cure is increasingly becoming a realistic goal. The advent of novel agents, with or without high-dose chemotherapy and autologous transplantation, uncovered a correlation between the depth of response to treatment and the outcome. Of note, minimal residual disease (MRD) negativity is increasingly shown to be associated with improved progression-free survival (PFS), and MRD status is becoming a well-established and strong prognostic factor. Here, we discuss the impact of MRD negativity on PFS and long-term disease control, as a surrogate for a potential cure in a significant proportion of patients. The MRD value and impact should be examined by focusing on different parameters: (i) sensitivity or lower limit of detection level (method used); (ii) timing of assessment and sustainability (iii) type and duration of treatment; (iv) initial prognostic factors (most importantly, cytogenetics) and (v) patient age. Currently, the highest probability of an operational cure is in younger patients receiving the most active drugs, in combination with autologous transplantation followed by maintenance therapy. Older patients are also likely to achieve operational cure, especially if they are treated upfront with an anti-CD38 antibody-based therapy, but also with novel immunotherapies in future protocols. The incorporation of MRD as a surrogate endpoint in clinical trials, would allow the shortening of these, leading to more personalised management, and achievement of long-term cure.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Sujoy Khan ◽  
Anirban Maitra ◽  
Pravin Hissaria ◽  
Sitesh Roy ◽  
Mahesh Padukudru Anand ◽  
...  

Urticaria is a common condition that occurs in both children and adults. Most cases have no specific allergic trigger and the aetiology of urticaria remains idiopathic and occasionally spontaneous in nature. Inappropriate advice such as avoidance of foods (milk, egg, prawn, and brinjal) is common place in certain sections of India mostly by nonspecialists that should not be routinely recommended. It is important to look for physical urticarias such as pressure urticaria in chronic cases, which may be present either alone or in combination with other causes. Autoimmune causes for chronic urticaria have been found to play an important role in a significant proportion of patients. Long-acting nonsedating antihistamines at higher than the standard doses is safe and effective. Quality of life is affected adversely in patients with chronic symptomatic urticaria and some may require multidisciplinary management.


2018 ◽  
Vol 13 (5) ◽  
pp. 815-822 ◽  
Author(s):  
Claudio Ponticelli ◽  
Francesco Locatelli

Glucocorticoids exert anti-inflammatory and immunosuppressive activities by genomic and nongenomic effects. The classic genomic effects are mediated by cytosolic glucocorticoid receptors that can upregulate the expression of anti-inflammatory proteins in the nucleus (transactivation) or repress the translocation of proinflammatory transcription factors from the cytosol into the nucleus (transrepression). The nongenomic effects are probably mediated by membrane glucocorticoid receptors. Glucocorticoid receptors are expressed also in podocytes and experimental data suggest that glucocorticoids may protect from podocyte injury. Glucocorticoids have a low therapeutic index and may exert a number of time-dependent and dose-dependent side effects. Measures to prevent or attenuate side effects include single-morning administration of short-acting glucocorticoids, dietetic counseling, increasing physical activity, frequent monitoring, and adapting the doses to the clinical conditions of the patient. Synthetic glucocorticoids, either given alone or in combination with other immunosuppressive drugs, are still the cornerstone therapy in multiple glomerular disorders. However, glucocorticoids are of little benefit in C3 glomerulopathy and may be potentially deleterious in patients with maladaptive focal glomerulosclerosis. Their efficacy depends not only on the type and severity of glomerular disease, but also on the timeliness of administration, the dosage, and the duration of treatment. Whereas an excessive use of glucocorticoids can be responsible for severe toxicity, too low a dosage and too short duration of glucocorticoid treatment can result in false steroid resistance.


Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 1933-1940 ◽  
Author(s):  
JW Mier ◽  
G Vachino ◽  
MS Klempner ◽  
FR Aronson ◽  
R Noring ◽  
...  

Abstract High concentrations of tumor necrosis factor (TNF) alpha have been detected in the plasma of patients undergoing immunotherapy with interleukin 2 (IL-2), suggesting that this cytokine may play a role in the fever and shocklike state induced by the administration of high- dose IL-2. Dexamethasone has been shown to inhibit the synthesis of TNF by monocytes activated in vitro by endotoxin. To determine if dexamethasone can exert a similar suppressive effect on IL-2-induced TNF synthesis in vivo, the concentration of TNF alpha was measured in plasma samples serially obtained (a) from cancer patients participating in a phase I dose escalation clinical trial with high-dose IL-2 administered in conjunction with dexamethasone (IL-2/Dex) and (b) from patients participating in concurrent studies with IL-2 alone. In contrast to the high plasma levels of TNF alpha detected in patients receiving IL-2 alone, TNF levels in most of the IL-2/Dex patients remained below the threshold of detectability of our TNF radioimmunoassay. The concurrent administration of dexamethasone also prevented the IL-2-induced increase in serum levels of C-reactive protein, a hepatic acute phase reactant whose synthesis is regulated by proinflammatory cytokines such as TNF. The steroid-treated patients also failed to develop the neutrophil chemotactic defect characteristic of IL-2 recipients. The concomitant administration of dexamethasone increased the maximum tolerated dose of IL-2 approximately threefold and markedly reduced the hypotension and organ dysfunction ordinarily observed in these patients. These results demonstrate that dexamethasone inhibits the release of TNF into the circulation of patients undergoing immunotherapy with IL-2. They further suggest that the altered spectrum and reduced severity of IL-2 side effects observed in patients receiving dexamethasone may be attributable in part to the suppressive effect of steroids on IL-2-induced TNF synthesis.


Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 1933-1940
Author(s):  
JW Mier ◽  
G Vachino ◽  
MS Klempner ◽  
FR Aronson ◽  
R Noring ◽  
...  

High concentrations of tumor necrosis factor (TNF) alpha have been detected in the plasma of patients undergoing immunotherapy with interleukin 2 (IL-2), suggesting that this cytokine may play a role in the fever and shocklike state induced by the administration of high- dose IL-2. Dexamethasone has been shown to inhibit the synthesis of TNF by monocytes activated in vitro by endotoxin. To determine if dexamethasone can exert a similar suppressive effect on IL-2-induced TNF synthesis in vivo, the concentration of TNF alpha was measured in plasma samples serially obtained (a) from cancer patients participating in a phase I dose escalation clinical trial with high-dose IL-2 administered in conjunction with dexamethasone (IL-2/Dex) and (b) from patients participating in concurrent studies with IL-2 alone. In contrast to the high plasma levels of TNF alpha detected in patients receiving IL-2 alone, TNF levels in most of the IL-2/Dex patients remained below the threshold of detectability of our TNF radioimmunoassay. The concurrent administration of dexamethasone also prevented the IL-2-induced increase in serum levels of C-reactive protein, a hepatic acute phase reactant whose synthesis is regulated by proinflammatory cytokines such as TNF. The steroid-treated patients also failed to develop the neutrophil chemotactic defect characteristic of IL-2 recipients. The concomitant administration of dexamethasone increased the maximum tolerated dose of IL-2 approximately threefold and markedly reduced the hypotension and organ dysfunction ordinarily observed in these patients. These results demonstrate that dexamethasone inhibits the release of TNF into the circulation of patients undergoing immunotherapy with IL-2. They further suggest that the altered spectrum and reduced severity of IL-2 side effects observed in patients receiving dexamethasone may be attributable in part to the suppressive effect of steroids on IL-2-induced TNF synthesis.


2020 ◽  
Vol 14 (2) ◽  
pp. 87-90
Author(s):  
Sadaf Amin Chaudhry ◽  
Nadia Ali Zafar ◽  
Rabia Hayat ◽  
Ayesha Noreen ◽  
Gulnaz Ali ◽  
...  

Background: Acne is the eighth most prevalent disease affecting 9.4% of the population worldwide and its prevalence in our country is estimated to be around 5%. Severe inflammatory acne is most likely to leave scars and in order to prevent facial disfigurement due to acne scarring, early treatment is desirable. Various treatment options have been formulated for acne, and are tailored according to the severity of the disease. Numerous clinical trials have been conducted till now, to determine the usefulness and side effect profile of such therapies, making acne treatment a highly studied area in dermatology. Objective of this study is to highlight the fact that oral Dapsone could be used as a cheaper alternate to isotretinoin in recalcitrant severe acne, especially in females where retinoids are sometimes contraindicated. Patients and methods: 51 patients, suffering from severe nodulocystic acne, fulfilling the criteria, were enrolled from the Department of Dermatology, Sir Ganga Ram Hospital, Lahore. All the study patients were given oral Dapsone 50mg for initial two weeks and then 100mg daily for the next 10 weeks along with oral cimetidine and topical clindamycin application twice daily. Investigator Global Assessment Scale (IGAS) was employed to measure effectiveness. The treatment was considered ʽeffectiveʹ if the patient achieves 2 or more than 2-grade improvement or almost clear or clear skin at the end of 12 weeks according to IGAS scale. The lesion counts were also done before the start of therapy (day 1) and at every two weeks follow up for 12 weeks. The change in lesion count observed between the baseline number and that seen at follow up visits was also used to evaluate the effectiveness of oral Dapsone. Safety was analyzed by fortnightly visits of the patients to look for any undesirable side effects and monitoring of the hematologic profile of the patients. Final follow up was done at the end of 16 weeks. Results: The study was conducted on 51 patients, with a ratio of 1:3 for males and females and a mean age of 25.2 years (SD ±5.81). At 12th week, patients had significant reduction in their acne lesions; with 7 patients (13.7%) showing completely clear skin, 17 patients (33.3%) had almost clear skin, 5 patients (9.8%) had 3-grade improvement. Twelve patients (23.5%) had 2-grade improvement from baseline score and only 2 patients (3.9%) had 1-grade improvement from baseline. Based on percentage reduction of lesions, excellent response was seen in 32 patients (62.7%), good response in 9 patients (17.6%), moderate response in 2 patients (3.9%), while no patient showed poor response. Dapsone was discontinued in 8 patients due to derangement of hematologic profile. Conclusion: Oral Dapsone, when given carefully, is a very effective therapeutic option in severe recalcitrant acne, with limited side effects.


2019 ◽  
Vol 21 (10) ◽  
pp. 734-748 ◽  
Author(s):  
Baoling Guo ◽  
Qiuxiang Zheng

Aim and Objective: Lung cancer is a highly heterogeneous cancer, due to the significant differences in molecular levels, resulting in different clinical manifestations of lung cancer patients there is a big difference. Including disease characterization, drug response, the risk of recurrence, survival, etc. Method: Clinical patients with lung cancer do not have yet particularly effective treatment options, while patients with lung cancer resistance not only delayed the treatment cycle but also caused strong side effects. Therefore, if we can sum up the abnormalities of functional level from the molecular level, we can scientifically and effectively evaluate the patients' sensitivity to treatment and make the personalized treatment strategies to avoid the side effects caused by over-treatment and improve the prognosis. Result & Conclusion: According to the different sensitivities of lung cancer patients to drug response, this study screened out genes that were significantly associated with drug resistance. The bayes model was used to assess patient resistance.


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